Effect of constant strain rate,composed of varying amplitudeand frequency, of early loading onperi-implant bone (re)modellingDe Smet E, Jaecques SVN, Jansen JJ, Walboomers F, Vander Sloten J, Naert IE.Effect of constant strain rate, composed by varying amplitude and frequency, of earlyloading on peri-implant bone (re)modelling. J Clin Periodontol 2007; 34: 618–624.doi: 10.1111/j.1600-051X.2007.01082.x.

AbstractAim: Examine the effect of varying components of strain rate – amplitude versusfrequency – while maintaining a constant strain rate of early controlled mechanicalloading on implant stability, peri-implant bone mass and bone-to-implant contact.

Material and Methods: Three groups of guinea-pigs received TiO2-blasted implantsin both tibiae. One week after installation test implants were loaded 5 days/weekduring 4 weeks. The contra-lateral implants were the unloaded controls. Strain rate waskept constant (1600me/s), while amplitude and frequency were varied per group.Implant stability was followed by resonance frequency analysis. Animals weresacrificed, and ground sections were prepared to rate bone-to-implant contact and bonemass.

Results: All implants (n 5 78) integrated uneventfully. A significant positive effect(p 5 0.03) of early loading on bone mass was observed in the distal medullar cavity. Asignificant difference in bone mass between test and control implants was evidencedbetween the groups (p 5 0.03 and 0.04). A significant increase in implant stability andbone-to-implant contact could not be shown.

Conclusions: Early controlled stimulation of peri-implant bone is related toamplitude/frequency and not to strain rate as such, considering a constant stimulationtime. An increase of bone mass around early-loaded implants was shown. This corticalbone model is most sensitive to low-frequency/high-amplitude stimulation.

Key words: animal study; early loading;frequency; guinea-pig; implant; strain; strainrate

Accepted for publication 18 February 2007

Currently in the clinic, there is a shifttowards faster implant loading. Thisresults in a decrease in discomfort forthe patients compared with the longhealing times in the delayed loadingprotocol. The local mechanical loadingsituation is believed to be a strongdeterminant in the processes of tissue

differentiation and bone formation/resorption around implants. Early/immediate loading might offer thepotential to stimulate osteogenic effectsduring implant healing under specificconditions. The present work is part ofa larger European Community – projectto analyse adaptive bone (re)modellingaround implants that receive controlledmechanical stimulation early post-opera-tively. The aim of this overall project(http://imload.mech.kuleuven.ac.be) isto develop a model of tissue differentia-tion that may predict the in vivo boneresponse on specific mechanical para-meters. With such a model, mechanical

stimulation parameters that accelerate orconsolidate osseointegration in cases ofearly and immediate loading can beselected or the design of the implantscan be optimized as a function of earlyand immediate loading.

Important parameters for osteogenic(bone forming) mechanical stimulationcan be identified from the literature (e.g.strain rate, peak strain, frequency, num-ber of cycles/duration) (Turner 1998). Inearlier guinea-pig experiments on earlycontrolled mechanical loading (De Smetet al. 2006), six groups with varyingstrain rates were compared. A signifi-cant positive effect of stimulation on

E. De Smet1, S. V. N. Jaecques2,J. J. Jansen3, F. Walboomers3,J. Vander Sloten2 and I. E. Naert1

1Department of Prosthetic Dentistry/BIOMAT

Research Group, School of Dentistry, Oral

Pathology and Maxillofacial Surgery, K. U.

Leuven, Kapucijnenvoer, Leuven, Belgium;2Department of Mechanical Engineering,

Division of Biomechanics and Engineering

Design, K. U. Leuven, Celestijnenlaan,

Leuven, Belgium; 3Department of

Biomaterials/Dentistry, University Medical

Center, University of Nijmegen, Nijmegen,

The Netherlands

Conflict of interests and source offunding statement

The authors declare that they have noconflict of interest.This research was funded by the EuropeanCommunity: IMLOAD QLK6-CT-2002-02442.

J Clin Periodontol 2007; 34: 618–624 doi: 10.1111/j.1600-051X.2007.01082.x

618 r 2007 The Authors. Journal compilation r 2007 Blackwell Munksgaard

peri-implant bone mass (BM) could beshown. However, the effect increasedwith decreasing strain rate of earlyloading, reaching an optimal osteogenicstimulus at a strain rate of 1600 me/s inthe cortical bone at a distance of 1.3 mmfrom the implant surface. An increase inperi-implant BM could be shown withincreasing force amplitude. Consideringstimulation frequency results were infavour of a low-frequency stimulation of3 Hz. In these experiments, the number ofcycles was kept constant, resulting invariable stimulation times. For the high-frequency stimulation groups, testimplants were only loaded 1 min./day,which could explain the lower osteogeniceffect. The benefit of high-frequencystimulation could be that lower forceamplitudes had to be applied, whichwere less manipulative, while resultingin a higher strain rate stimulation.

The hypothesis of the present studywas that well-controlled implant loadingdoes lead to an improved bone-healingresponse, considering more and acce-lerated peri-implant bone formation,resulting in an accelerated increase inimplant stability.

The a priori goal of this guinea-pigstudy was to identify the effect of earlyload strain rate ( 5 frequency � strain)versus strain/frequency of a sinusoidalvarying load. The strain rate was keptconstant for the three groups, while theamplitude and frequency were varied inan inversely proportional manner. If strainrate is the determining factor of earlycontrolled mechanical loading, no differ-ence in implant stability, peri-implant BMand bone-to-implant contact should beexpected between the three groups.

Material and Methods

Surgical procedure

Three series of male, skeletally matureguinea-pigs (n 5 13 on average per ser-ies) received one percutaneous custo-mized Ti implant (Astra Tech,Molndal, Sweden) in the distal part ofboth tibiae. Surgery was performedunder general injection anaesthesia[Ketamine Ceva 1000s (Ceva AnimalCare, Brussels, Belgium) 50 mg/kg i.m.and Xyl-Ms (V. D. K., Arendonk,Belgium) 2% sol. 0.25 ml/kg i.m.]. Alongitudinal incision was made on themedial side of the tibia just above theankle joint. Both cortices of the tibiawere perforated with low rotationalspeed under continuous external salinecooling to a diameter slightly smaller

(0.3 mm) than the implant’s diameter toobtain a good primary stability of theimplants. Implants were inserted bymanual torque. Resorbable sutures(Vicryls 3–0, Ethicon GmbH, Norder-stadt, Germany) were used to close thelongitudinal incisions (investigator E.D.). Post-operatively, the guinea-pigsreceived doxycycline (Vibravets, Pfi-zer, Belgium) (0.5 mg/kg p.o.) for 5days to prevent infection. Additionally,strict cage hygiene was maintained bychanging the bedding material dailyduring the study period. Buprenorfin(Temgesics, Reckit & Coleman, UK)(0.05 mg/kg s.c.) was used as analgesia.

Implants

Customized screw-shaped TiO2-blasted(Ra: 1.74 m) Ti6Al4V implants(1.8 � 5 mm) (Astra Tech) were used(Fig. 1). The percutaneous part was coni-cally shaped and allowed a tight connec-tion of the Osstell transducer andstimulation device by screw tightening.

Mechanical stimulation

Skin healing was allowed for 1 weekafter implant installation. Implants wereallocated at random in the right or lefttibia of the guinea-pig as a test orcontrol implant. The control implantswere unloaded, while the test implantsreceived a sinusoidal varying bendingmoment with a force-controlled electro-mechanical shaker (Model 4810, Brueland Kjaer, Naerum, Denmark). All testimplants of the three groups received aconstant stimulation period of 10 min./day, 5 days/week, for four successiveweeks. The strain rate of the mechanicalstimulation was set at 1600 me/s as anoptimum from earlier results (De Smetet al. 2006) for all three groups, whileforce amplitude and stimulation fre-quency were varied in an inverselyproportional manner. The number ofcycles was adjusted so that the stimula-tion time was kept constant for 10 min.in all three series, with a minimum of1.800 cycles (Kaspar et al. 2002). Thestrain rates listed in Table 1 were calcu-

lated from cadaver strain gauge mea-surements, with the strain gauge gluedon the outer surface of the tibial bone inthe direction of the stimulation lever arm,at a 1.3 mm distance from the implantsurface (Fig. 2a–c). During stimulation,the animals were under full inhalationanaesthesia (Fluothanes, halothane, Zene-ca, Belgium/Forenes, isoflurane, Abbott,UK) and the hind leg was firmly fixed toensure reproducible mechanical stimula-tion. The horizontal lever was attachedonto the implant, in alignment with thelong axis of the tibia. Thus, the forcesacted parallel to the long axis of theimplants. At a distance of 20 mm distallyfrom attachment point, the electro-mechanical shaker applied the sinusoidallyvarying force through a piezo load cell(model PCB 208B03, PCB Piezotronics,Depew NY, USA). Force was transferredfrom the load cell to the lever through anadjustable pin. A preload of approximately1 N ensured continuous contact with thelever. Signals from the load cell wereamplified by a PCB 480D06 amplifier(10 s time constant) (PCB Piezotronics)and captured by a Keithley 1702AO 12A/D data acquisition card (Keithley Instru-ments B.V., Sint-Pieters-Leeuw, Belgium).The same card was also used to send the

Fig. 1. Customized Ti6Al4V implants(1.8 � 5 mm) (Astra Tech) TiO2-blastedresulting in an Ra value of 1.74mm.

Table 1. Mechanical loading parameters of the early stimulation experiment of screw-shapedTiO2-blasted Ti6AL4V implants in the distal tibia of the guinea-pig model

Group Cycle no. (n) Force amplitude (N) Strainamplitude (me)

Frequency (Hz) Strainrate (me/s)

1 (n 5 10) 1800 2 533 3 16002 (n 5 14) 6000 0.6 160 10 16003 (n 5 15) 18000 0.2 53 30 1600

n, number of guinea-pigs.

Strain rate effect on peri-implant bone 619

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control signal for the shaker through a DC-coupled power amplifier (custom made).Control software, including a force-con-trolled feedback loop, data acquisition anddata visualization, was implemented as aTestPoint application on a Pentium-100PC (Dell, Bracknell, UK) running underMS Windows 95. Normal cage activitywas allowed between the loading sessions(investigators E. D. and S. J.)

Stability measurements

To rate the stability of the implantfixation, the principle of vibration ana-lysis, as commercially available throughthe Osstells device (Integration Diag-nostics, Savedalen, Sweden), was used.A customized transducer was manufac-

tured by the latter to fit the percutaneouspart of the implant. For group 1, implantstability measurements were performedat implant installation, 1 week after andfrom then on every 2 weeks, for test aswell as for control implants. For theother groups 2 and 3, the protocol wasadjusted to follow the implant stabilityweekly (investigator E. D.)

The protocols for all guinea-pigexperiments were approved by the ethi-cal committee of the Animal ResearchFacility of the KULeuven.

Specimen preparation

At the end of the fourth week ofmechanical stimulation, animals weresacrificed. Post-mortem bone segments

were fixed in 10% buffered formalinsolution. Subsequently, serial groundsections were prepared (Van Der Lubbeet al. 1988, Klein et al. 1994). Thesections (n 5 3 per implant) were cutin the loading direction parallel to thelong axis of the tibia and the implant.The sections were stained with methy-lene blue and basic fuchsin for histologyand morphometric analysis.

Histological analysis

A light microscope (Leica Microsys-tems GmbH, Wetzlar, Germany) wasused for the histological evaluation deal-ing with a general description of thetissues surrounding the implants.

0

800

600

400

200

1800

1600

1400

1200

1000

0 1 2 3 4 5 6 7Force (N)

Stra

in (

µstr

ain)

F = (6N)

20 mm2100

µε

a b

c

y=260.19x + 10.932R2=0.9973

Fig. 2. (a) Strain gauge (white arrow) attached to guinea-pig tibia at a distance of 1.3 mm from the implant (cadaver calibration experiment).(b) Measured strain as a function of the amplitude of the force applied by the mechanical stimulator on the 20 mm long lever. The strainsincrease linearly with the force amplitude. This ex vivo calibration experiment was performed three times on one dissected guinea-pig tibia.(c) Simplified finite element model of part of a guinea-pig tibia with a cylindrical implant showing bone strains of 2000–3000me (yellow) inthe cortical bone in the immediate vicinity of the implant for a force of 6 N applied on a lever of 20 mm attached on the implant.

620 De Smet et al.

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Histomorphometrical analysis

The histomorphometrical analysis wascarried out by means of a light microscope(Microsystems GmbH) connected to a PC,equipped with a video and image analysissystem (Leica Q-wins Pro-image analysissystem, Wetzlar, Germany). Digitalimages were made of the proximal anddistal half of the histological section. Aroutine was written in the program forstandardized segmentation of the bone onthe digital images of the histological sec-

tions. Determination of the regions ofinterest allowed manual adjustments. Allquantitative measurements were based onthe average of three sections per implant.The following histomorphometrical ana-lyses were carried out:

1. Total bone contact (TBC) (%) 5[total length of bone contact (mm)/total length of implant surface(mm)] � 100, along the proximaland distal implant surfaces.

2. BM (%) 5 [area of bone in the refer-ence area (mm2)/reference area(mm2)] � 100.

Based on the BM, the difference inBM (d BM) between test and controlside was calculated. Quantification ofBM (%) was performed for both theupper and lower cortices and the medul-lar cavity at 500, 1000 and 1500mmfrom the proximal and distal implantsurfaces (Fig. 3) (investigator E. D.).

Statistical analysis

The histomorphometrical data were ana-lysed by fitting a linear mixed modelwith an appropriate variance – co-var-iance matrix to account for the correla-tion between measurements on the sameguinea-pig (test/control). The modelincluded group, stimulation and theirinteraction as fixed effects. A Tukeytest adjusted for multiple testing ata5 0.05.

Results

Animal and implant outcome

All animals survived well during thecourse of the experiment. Owing to the1-week-healing period of the skin, pre-ceding the implant stimulation regimen,the skin remained healthy during thewhole course of the experiment. All,test and control implants (n 5 78), inte-grated uneventfully. At sacrifice, noclinical mobility of any of the implantscould be evidenced.

–15

–10

–5

0

5

10

15

20

25

C500 C1000 C1500 M500 M1000 M1500 A500 A1000 A1500

Region

Del

ta b

onem

ass

(%)

Group 1Group 2Group 3

**

Fig. 4. Mean bone mass (BM) (%) quantification was performed for both the upper (C) and lower (A) cortices and the medullar (M) cavity500, 1000 and 1500mm from the proximal and distal implant surfaces. Based on the BM, the difference in BM between the test and controlsides [d BM (%) 5 BM at the stimulated minus BM at the control side] was calculated for the three groups and presented here for all regions atthe distal and proximal sides. A significant difference in d BM between Groups 1 and 2 (p 5 0.03)/Group 3 (p 5 0.04) for the M500 region wasevidenced. For the M1000 and M1500 region, nor for the cortical (cervical and apical) regions of interest, a statistically significant differencein d BM between the groups was shown.

C AMC AM

500 µm

1000 µm

1500 µm

Fig. 3. Quantification of bone mass (%) was performed on digital images of the proximal anddistal half of the histological slices, at 3 � 3 regions of interest (ROI): at 500, 1000 and1500mm from the proximal and distal implant surfaces for the cervical cortex (C500, C1000,C1500), the medullar cavity (M500, M1000, M1500) and for the apical cortex (A500, A1000,A1500).

Strain rate effect on peri-implant bone 621

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Bone mass

On the histological slices, new bone isformed along the implant surface in themedullar cavity. Not only along theimplant surface but also along the endo-steum away from the implant new boneis formed in the medullar cavity. Thearea of new bone formed from thecervical endosteum is systematicallylarger than along the apical endosteum.Systematically more re-modelled bonecould be seen at the cervical than at theapical cortex, both for test and controlimplants.

Histomorphometry showed a signifi-cant effect of stimulation on BM(p 5 0.03) at the distal side of theimplants. A significant difference in dBM between groups 1 and 2 (p 5 0.03)/group 3 (p 5 0.04) for the M500 regionwas evidenced. No effect of stimulationand of group could be shown for theregions M1000 and M1500 (Fig. 4).

Bone contact

The average percentages (SEM) ofbone-to-implant contact along the prox-imal and distal surfaces of test andcontrol implants ranged between 65.3(1.68) and 87.70 (3.01) (Table 2).Despite a tendency, there was neither asignificant difference in total bone-to-implant contact between the compres-sion (distal) and the tensile (proximal)sides, nor between the test and controlimplants, or among the different series.

Implant stability

Initial implant stability ranged betweena mean peak resonance frequency of5.100 and 5.500 Hz depending on thegroups (Fig. 5a–c). Statistically signifi-cant differences were neither foundbetween the test and control implantsnor between the groups, or over time.

Discussion

To explain bone adaptation to mechan-ical loading, Frost’s mechanostat (Frost

1987) focused on bone strain amplitude.He described a window of mechanicalusage, which is defined by an upperboundary (1500 mstrain), called theminimum effective strain above whichbone undergoes modelling and changesits structure in order to reduce the localstress and strain (Frost 1983). It hadbeen shown that above a certain strainthreshold, bone formation is initiated incortical bone (Rubin & Lanyon 1985,Turner et al. 1994) and that withincreasing strain, bone responds withincreasing formation activity (Hsieh etal. 2001). Excessive load has been stu-died and even the borderline of thebone-implant failure value has beenquantified in the rabbit model (Duycket al. 2001). The strain estimated fromCT-based finite element models asso-ciated with overload induced resorptionwas 4200 mstrain/s. Frost (1992) consid-ered 4000mstrain a possible thresholdfor pathological bone overload, suggest-ing that higher strains would lead to theaccumulation of bone micro-damage(micro-cracks) in case of cyclic load.In the guinea-pig experiments, anincrease in d BM between test andcontrol peri-implant bone could beshown with increasing force amplitude(De Smet et al. 2006). From a genericfinite element calculation of this guinea-pig implant model (Fig. 2c), it wasestimated that a force amplitude of 6 Ncauses peri-implant bone strains inthe order of magnitude of 2000–3000 mstrains next to the implant, whichshould be considered an osteogenic sti-mulus according to Frost’s mechanostat(Frost 1987). From this simplified finiteelement, it is obvious that the higheststrains are observed next to the implantsurface (ROI 500mm). Further awayfrom the implant, the strain decreases,resulting in less pronounced d BM.

It has been shown that bone respondsespecially to dynamic rather than staticloads (Duyck et al. 2001, Robling et al.2001). This means that cortical boneadaptation is not solely dependent on

strain amplitude, but that cyclic loadshave the potential to induce bone for-mation (Jagger et al. 1995). Mechanicalstimulus parameters such as strain rate(Mosley & Lanyon 1998), frequency,number of loading cycles (Turner et al.1994, Robling et al. 2002) and straindistribution and gradient (Judex et al.1997), will all influence the corticalbone-adaptive response. Strain rate canfurther be decomposed into strain ampli-tude and loading frequency. A positiverelationship between loading frequencyand bone formation has been demon-strated in several studies (Rubin &McLeod 1984, Hsieh & Turner 2001).

In this model, although the samestrain rate was applied, the effect ofearly mechanical stimulation decreasedwith decreasing force amplitude andincreasing frequency. In the ulna axialcompression model in mice, a dose–response relationship between loadingfrequency and cortical bone adaptationreaching a plateau with frequenciesbeyond 10 Hz has been shown (Warden& Turner 2004). The mechanism for thisnon-linear frequency response is notknown, but the authors also confirmed,based on strain gauge measurements,that no dampening of the mechanicalloading associated with high-frequencyloading occurred. For the high-fre-quency group of the guinea-pig experi-ments, d BM reaching a plateau couldnot be shown, but instead our resultsshowed a lower effect of high-frequencymechanical stimulation than for the 3 Hzfrequency stimulation protocol. Usingthe rat tibia four-point bending model,cortical bone responded to frequenciesof 0.5 Hz and above, but not to lowerfrequencies (Turner et al. 1995). Morerecently, using the rat ulna axial loadingmodel, it was found that cortical boneformation increased successively withincreasing loading frequency up to10 Hz (Hsieh & Turner 2001). Bonehealing around a roughened implantwas found to be improved by loadingthe functionally isolated turkey ulna at afrequency of 20 rather than 1 Hz (Rubin& McLeod 1984). These data seem toindicate that an increase in loadingfrequency results in an increase in anadaptive response of cortical bone.

However, the effects of frequencyshould not be isolated from the effectsof the cycle number (Kaspar et al. 2002).At a constant frequency, the proliferateresponse of human bone-derived growncells increased with the number ofapplied cycles until a maximum of 1800

Table 2. Mean bone-to-implant contant (%) (SEM) of test and control implants, for the distal andproximal surface, for the three guinea-pig series

Group Test Control

distal proximal distal proximal

1 (n 5 10) 78.6 (1.9) 65.34 (1.7) 76.65 (3.0) 65.32 (3.0)2 (n 5 14) 87.7 (3.0) 84.01 (2.4) 79.03 (2.9) 77.83 (2.8)3 (n 5 15) 79.2 (2.9) 67.7 (2.0) 65.17 (1.6) 69.71 (2.5)

n, number of guinea-pigs.

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cycles was reached. Data suggest that thenumber of applied load cycles within agiven time frame plays an important rolein bone structural adaptation in vivo(Rubin & Lanyon 1984).

Recent research has shown trabecularbone to be responsive to very low-magnitude mechanical stimuli (0.3 g/5 mstrain) introduced at a high frequency(30 Hz) (Rubin et al. 2001, 2002). It ispossible that the mechano-transductivepathways in cortical and trabecular bonediffer and that the pathways responddifferently to an equivalent mechanicalstimulus. Nowadays, several reportssuggest that osteocytes, which are term-inally differentiated osteoblasts and thatare present throughout the entire miner-alized bone matrix, are the primarycandidates for bone mechano-sensing

(Weinbaum et al. 1994, Cowin et al.1995, Burger & Klein-Nulend 1999). Inparticular, it is hypothesized that boneinterstitial fluid flow through the cana-licular network, which is induced byfluid pressure gradients in the deformingbone matrix, activates certain intra-cel-lular processes in the osteocytes. Bio-chemical signals, released by theosteocytes, would then in turn regulateosteoblastic and osteoclastic activity(Burger & Klein-Nulend 1999).

A significant positive effect ofmechanical stimulation on bone-to-implant contact could not be shown inthis study, although there was a trend formore bone-to-implant contact at thecompressive (distal) versus tensile(proximal) side for the mechanicallystimulated implants versus the controls.

This is in agreement with data fromanother study with different implantgeometry (De Smet et al. 2006). More-over, hardly any change in implantstability measured by RF could be evi-denced. This could be due to the bicorticalfixation of the implants in the tibial bone,which was already high initially at implantinstallation. In a clinical study using RFA,Barewal et al. (2003) neither showedsignificant changes in implant stabilityduring a 10-week period after implantinstallation for implants installed in TypeI bone (Lekholm & Zarb 1985). However,a numerical simulation study and in vitromeasurements for the guinea-pig experi-ments showed that the transducer orienta-tion, the part of the bone around theimplant and the boundary conditions (fixa-tion of the tibia), influences the resonancefrequency value measured by the Osstellsystem (Pattijn et al. 2007). In the guinea-pig model where the conditions deviatestrongly from those in human dental prac-tice, the Osstell technique does not allowthe comparison of the stability betweendifferent implants due to poor repeatabilityand to the fact that the resonance fre-quency is determined by the whole bone–implant–transducer system and not onlyby the quality of the bone–implant inter-face (Pattijn et al. 2006).

This study explored a potential animalmodel showing that the in vivo forcecan be controlled experimentally to studyquantitative biomechanical-mediatedbone adaptation under various loadingsituations. Eventually, this may lead to abetter understanding of improved earlyloading protocols of oral implants inhumans. Differences in bone re-model-ling rates between guinea-pig andhumans can limit the extrapolation ofthe present data. Interpretation of animaldata to humans needs to be carefullystudied. Therefore, suggested principlesof bone adaptation should be simulatedfirst on individualized finite elementmodels and validated to the results ofthe animal experiment before these canbe considered for extrapolation to bonetissue application in humans.

While in these experiments the strainrate was kept unchanged, in a subse-quent study the frequency will be keptconstant. The latter will help us learnmore about the importance of the forceamplitude at low-frequency stimulation.

Conclusion

The present data show an optimi-zation of the BM around controlled

Group 1

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Control

Group 2

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Group 3

47004800490050005100520053005400550056005700

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Fig. 5. Mean resonance frequencies (Hz) of test and control implants in the three groups.Stability analysis was performed at implant installation and from then on weekly (for series 1every 2 weeks from the start of stimulation). Significant differences were found neitherbetween test and control implants nor between the groups.

Strain rate effect on peri-implant bone 623

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early-loaded implants. The effect of earlymechanical stimulation of peri-implantbone is strongly dependent on the strain/frequency and not on the strain rate assuch for a constant period of stimulation.This cortical bone model has been shownto be most sensitive to low-frequency/high-amplitude stimulation.

Acknowledgements

S. Goovaerts and J. Vanhulst (Depart-ment of Biomechanics & EngineeringDesign; Metallurgy & Materials Engi-neering, KU Leuven) are acknowledgedfor technical support.

S. Cecere (Biostatistical Centre, Schoolof Public Health, Leuven, Belgium) isacknowledged for the statistical analysis.

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Address:

I. E. Naert

Department of Prosthetic Dentistry/BIOMAT

Research Group

School of Dentistry

Oral Pathology and Maxillofacial Surgery

Faculty of Medicine

K. U. Leuven

Kapucijnenvoer 7, 3000 Leuven

Belgium

E-mail: Ignace.Naert@med.kuleuven.be

Clinical Relevance

Scientific rationale: Today, there is ashift towards faster implant loading.Local loading is believed to bestrongly determine the processes ofbone formation/resorption aroundimplants.

Principal findings: This animal studyshows that early loading does notimpair implant healing and that strainrate is not the determining parameter.Early mechanical stimulation, withan optimal low frequency (3 Hz)/high amplitude (2 N), increasesperi-implant bone mass.

Practical implications: Differencesin re-modelling rates between ani-mals and humans need careful inter-pretation. Once the influence ofmechanical parameters is under-stood, a general model for adaptivebone re-modelling can be applied tothe human jawbone.

624 De Smet et al.

r 2007 The Authors. Journal compilation r 2007 Blackwell Munksgaard